Previously Applicants have found that dry powder comprising aerodynamically light particles are suitable for inhalation of drugs into the lungs. However, there are several problems associated with the aerosol delivery of therapeutic, diagnostic and/or prophylactic agents (hereinafter collectively referred to as drug). For example, electrostatic charge interactions influence the overall efficiency of delivery of dry particles via a Dry Powder Inhaler (DPI), since such forces are considered to be significant for attraction and adhesion between the particles themselves as well as between the particles and the device surface. Additionally, particle size distribution, particle morphology, and moisture content can greatly influence the bulk properties of a dry powder formulation and its performance.
In the case of dry powders comprising aerodynamically light particles, appropriate criteria and tests must be instituted to control parameters considered to be key to ensuring reproducibility of the physicochemical properties of the drug containing particles. Key specification parameters may include color, appearance (visual and microscopic), moisture, melting range, particle size distribution, surface area, form(s), and residual solvents. Specifications for control of particle size distribution and forms (e.g., shape, texture, surface) of the drug containing particles are parameters often used to predict reproducible drug product performance.
The composition of a formulation to be administered via a DPI has a direct effect on the stability of the formulation as well as on the dosing performance of the product. The suitability of a dry powder particulate composition is dependent on its chemical and physical characteristics, which can have direct effect on the performance of the product (e.g., ease of entrainment of the formulation, energy input necessary for dispersion and aerosolization, hygroscopicity of the formulation). For example, aggregation of dry powder particles may affect the particle size distribution of the emitted drug substance, the homogeneity of the drug substance, the aerodynamic properties of the dry powder particles in the device, and hence the delivered dose.
For DPI's, the target formulation fill weight is important yet it can be deceptive if the particle delivery is variable due to varying levels of aggregation of cohesive particles. Particles produced for inhalation, which are typically small in size (geometric diameter of 1 to 5 μm), tend to stick together.
Edwards et al. (U.S. Pat. No. 5,985,309)(hereinafter referred to as “Edwards”) discloses advantages of aerodynamically light particles for drug delivery to the pulmonary system. Edwards use of larger particles (i.e., mass median diameter of at least about 5 microns) is advantageous since they are able to aerosolize more efficiently than smaller, denser aerosol particles such as those currently used for inhalation therapies.
Thus, there is a need for improved pharmaceutical compositions suitable for pulmonary administration delivered via a dry powder inhaler with improved aerosolization properties and optimized particle-particle interactions. In particular, there is a need for dry powder pharmaceutical compositions which are highly dispersible and which efficiently emit and penetrate into the lungs from a dry powder inhaler.